Cancer Control Research
1R03CA059241-01
Barlow, William E.
MARKERS OF FUTURE BREAST CANCER RISK IN BIOPSIED WOMEN
AbstractMortality from invasive breast cancer has remained high, despite advances
in early detection, diagnosis and treatment. Identification of women at
high risk could result in targeted prevention efforts. Women who have
undergone previous breast biopsy but were not positive for cancer at that
time, are believed to be at elevated risk for future breast cancer,
particularly if certain types of benign conditions were present at time
of biopsy. This project proposes to apply new techniques to analyze
biopsied material and identify potential biologic markers, thus
sharpening criteria for determination of increased risk of invasive
breast cancer.
Biopsied material characteristics, individually and in combination, will
be evaluated as markers among women who have undergone a previous breast
biopsy. These characteristics include measures of cellular
characteristics (histologic type, S-phase fraction, and ploidy) and
control mechanisms (receptors, proliferating cell nuclear antigen (PCNA),
oncogene expression, and cathepsin-D). Ploidy and S-phase fraction will
be assessed by flow cytometry on tissue samples collected at the time of
initial breast biopsy. Cathepsin-D, PCNA, cerbB-2 expression, and
estrogen and progesterone receptors will be assessed by
immunocytochemical techniques.
The population consists of women aged 40 and older enrolled in the Breast
Cancer Screening Program (BCSP) of a large HMO. Since 1985, 87,892 women
have enrolled in the BCSP and have completed a comprehensive
questionnaire regarding breast cancer risk factor information. Attention
is restricted to 2,734 women who had a non-positive breast biopsy
performed since 1984. An estimated 67 women were subsequently diagnosed
with invasive disease. Biologic markers for this group and an equal
number of control women will be compared in a case-cohort study. This
design emulates a cohort study but reduces the number of tissue samples
to be evaluated. The independent contribution of each marker will be
tested after controlling for potential confounders, such as age, family
history, parity, and hormonal information. The impact of type of benign
breast disease and screening history will also be evaluated. It is
hypothesized that the rate of cell growth and presence or absence of
control mechanisms will augment risk information conveyed by benign
breast disease type and will enhance estimation of risk of future
invasive breast cancer.
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